Pathologic complete response to preoperative chemotherapy predicts cure in early-stage non-small-cell lung cancer: combined analysis of two IFCT randomized trials.

INTRODUCTION: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy resulted in improved outcome, and to determine predictive factors for pCR. METHODS: Eligible patients with stage-IB or -II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique phase-III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. RESULTS: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival was 80.0% compared with 55.8% in the non-pCR group (p = 0.0007). In multivariate analyses, pCR was a favorable prognostic factor of overall survival (relative risk = 0.34; 95% confidence interval = 0.18-0.64) in addition to squamous-cell carcinoma, weight loss less than or equal to 5%, and stage-IB disease. Five-year disease-free survival was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p < 0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (odds ratio [OR] = 4.30; 95% confidence interval = 1.90-9.72). CONCLUSION: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in stage-IB-II NSCLC. Our study is the largest published series evaluating pCRs after preoperative chemotherapy. The only factor predictive of pCR was squamous-cell carcinoma. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

BACKGROUND: Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. METHODS: In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. FINDINGS: 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]). INTERPRETATION: Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. FUNDING: Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer.

[Metastatic non-small cell lung cancer: Systemic treatment of patients aged 70 and over]. / Cancer bronchique non à petites cellules métastatique : les traitements systémiques des sujets de plus de 70 ans.

Patients aged 70 and over represent the third of the population of patients with lung cancer. There has been for a long time a certain nihilism regarding the treatment of elderly patients with advanced lung cancer as well from medical doctors but also from families and patients themselves with the false belief of an indolent course of the disease in elderly patients. As a result, clinical trials devoted to elderly patients were quite scarce until the end of the last decade. Nevertheless, an important trial was published in 1999 with the comparison of vinorelbine as a single agent versus best supportive care only in patients aged 70 and over with an advanced non-small cell lung cancer. The survival benefit with vinorelbine was important. Then two trials were published comparing monotherapy with either vinorelbine or gemcitabine to the doublet vinorelbine and gemcitabine without convincing results. As a consequence, the ASCO 2004 recommendations were to treat elderly patients with a monotherapy (gemcitabine or vinorelbine). Recently an IFCT trial was presented at the plenary session of the ASCO 2010. A carboplatin (every 4weeks)+weekly paclitaxel doublet was compared to a vinorelbine or gemcitabine (choice of the center). The survival benefit was of such magnitude that the paradigm of treatment of elderly patients PS 0-2 with advanced NSCLC should be modified in favor of the tested doublet. There should be a reappraisal of the geriatric indexes recommended by the oncogeriatricians regarding their exact prognostic or predictive role.

Severe pulmonary hypertension and chronic obstructive pulmonary disease.

RATIONALE: Severe pulmonary hypertension occurs occasionally in patients with chronic obstructive pulmonary disease (COPD), but no detailed description of these patients is available. OBJECTIVES: To identify and characterize patients with COPD and severe pulmonary hypertension. METHODS: Retrospective study of 27 patients with COPD with severe pulmonary hypertension (pulmonary artery mean pressure [Ppa], > or = 40 mm Hg) among 998 patients who underwent right heart catheterization between 1990 and 2002 as part of a workup for chronic respiratory failure during a period of disease stability. RESULTS: Of the 27 patients, 16 had another disease capable of causing pulmonary hypertension. The remaining 11 (11 of 998, 1.1%) patients had COPD as the only cause of pulmonary hypertension, with a median Ppa of 48 mm Hg (interquartile range, 46-50). They had an unusual pattern of cardiopulmonary abnormalities with mild to moderate airway obstruction, severe hypoxemia, hypocapnia, and a very low diffusing capacity for carbon monoxide (p < 0.01 compared with a control group of patients with COPD). Exertional dyspnea was more severe (p < 0.01) and survival was shorter (p = 0.0026) than in the control subjects. CONCLUSIONS: Severe pulmonary hypertension is uncommon in patients with COPD. When it occurs, another cause must be sought. COPD with severe pulmonary hypertension and no other possible cause shares features with pulmonary vascular diseases, such as idiopathic pulmonary hypertension.

First line chemotherapy with gemcitabine in advanced non-small cell lung cancer elderly patients: a randomized phase II study of 3-week versus 4-week schedule.

PURPOSE: This randomized phase II multicenter trial aimed at evaluating the efficacy and safety of the 4-week versus 3-week schedules of gemcitabine monotherapy in previously untreated elderly patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients with stage IIIB or IV NSCLC, and age between 70 and 90 years, were randomized to receive gemcitabine dose of either 1000 mg/m2 on days 1, 8, 15, every 28 days (arm Q4W), or 1125 mg/m2 on days 1 and 8, every 21 days (arm Q3W). RESULTS: From June 1999 to January 2001, 81 patients (42 on arm Q4W; 39 on arm Q3W) were included. The median age was 75 on both arms; most patients (82.7%) were male, and had a Karnofsky performance status of 80 or 90 (76.5%). For arms Q4W and Q3W, respectively, the median time to treatment failure was 83 days (95% CI, 69-98 days) versus 92 days (95% CI, 63-113), and the median survival was 154 days (95% CI, 108-227) versus 205 days (95% CI, 125-344). The objective response rate was higher on arm Q3W (28.2%) than on arm Q4W (14.3%). Total number of cycles administered was 132 on arm Q4W (median 3, range 1-10 cycles) and 169 on arm Q3W (median 4, range 1-9 cycles). Patients on arm Q4W and Q3W, respectively, received 100.1 and 99.8% of the planned weekly mean dose. The most common grade, three to four toxicities, was neutropenia (17.1% on arm Q4W versus 18.9% on arm Q3W) and thrombocytopenia (12.2% on arm Q4W versus 2.6% on arm Q3W). CONCLUSION: Although both 3- and 4-week gemcitabine regimens were safely and effectively administered in chemonaive elderly patients with advanced NSCLC, the 3-week schedule appears to be the more convenient for this population. Moreover, even if this is only a phase II study this 3-week schedule appears to be at least as efficient as the 4-week regimen.